EA Laboratoire d'Immunovirologie et Polymorphisme Génétique, Université de Nantes, France.
AIDS. 2011 Sep 10;25(14):1701-10. doi: 10.1097/QAD.0b013e328349a437.
In phase I/II trials, IL-7 immunotherapy has been shown to expand CD4(+) T cells. However, expression of the IL-7 receptor α-chain, CD127, is reduced on CD4(+) T cells from HIV-positive patients, and defects in CD127 signaling have also been reported. To refine and improve cytokine immunotherapy, it is important to identify stimuli that can restore proliferation of CD4(+) cells with defective responses to IL-7.
Observational study comparing viremic HIV-positive patients with HIV-negative controls.
Peripheral blood mononuclear cells were cultured in the presence of 1 nmol/l IL-2, IL-7, IL-15 or RLI (an IL-15Rα/IL-15 fusion protein). Proliferation of different T-cell subsets was assessed by carboxyfluorescein succinimidyl ester fluorescence. Expression of CD127 on CD4(+) T-cell subsets was also analyzed.
In HIV-positive patients, CD127 expression was correlated with CD4(+) T-cell count in the CD4(+)(N) (R(2) = 0.36; P < 0.01) and CD4(+)(CM) (R(2) = 0.45; P < 0.001) populations, whereas CD127 expression on CD4(+)(EM) cells was significantly reduced in HIV-positive individuals compared with controls (P = 0.001) independently of CD4(+) T-cell count. In patients with high CD4(+) T-cell counts, proliferation in response to IL-7 was significantly reduced only in CD4(+)(EM) cells (P < 0.05). RLI, and to a lesser extent IL-15, induced strong proliferation of CD4(+)(EM) cells from both HIV-positive patients and controls. Neither agent stimulated proliferation of CD4(+)(N) or CD4(+)(CM) cells.
In HIV-positive patients, CD4(+)(EM) cells are deficient in both CD127 expression and proliferation in response to IL-7. RLI and IL-15 specifically induced proliferation of CD4(+)(EM) cells, suggesting that they may have a unique potential to complement IL-7 immunotherapy.
在 I/II 期临床试验中，IL-7 免疫疗法已被证明可扩增 CD4+T 细胞。然而，HIV 阳性患者的 CD4+T 细胞上表达的 IL-7 受体α链（CD127）减少，并且也报道了 CD127 信号传导的缺陷。为了改进和优化细胞因子免疫疗法，确定可以恢复对 IL-7 反应有缺陷的 CD4+细胞增殖的刺激物非常重要。
比较病毒血症 HIV 阳性患者和 HIV 阴性对照的观察性研究。
外周血单核细胞在 1nmol/L IL-2、IL-7、IL-15 或 RLI（IL-15Rα/IL-15 融合蛋白）的存在下培养。通过羧基荧光素琥珀酰亚胺酯荧光评估不同 T 细胞亚群的增殖。还分析了 CD4+T 细胞亚群上 CD127 的表达。
在 HIV 阳性患者中，CD127 的表达与 CD4+（N）（R2=0.36；P<0.01）和 CD4+（CM）（R2=0.45；P<0.001）细胞群中的 CD4+T 细胞计数相关，而与对照组相比，HIV 阳性个体的 CD4+（EM）细胞上的 CD127 表达显著降低（P=0.001），而与 CD4+T 细胞计数无关。在 CD4+T 细胞计数较高的患者中，仅在 CD4+（EM）细胞中对 IL-7 的反应性增殖明显降低（P<0.05）。RLI，并且在较小程度上 IL-15，诱导来自 HIV 阳性患者和对照的 CD4+（EM）细胞的强烈增殖。两种试剂均未刺激 CD4+（N）或 CD4+（CM）细胞的增殖。
在 HIV 阳性患者中，CD4+（EM）细胞在 CD127 表达和对 IL-7 的反应性增殖两方面均存在缺陷。RLI 和 IL-15 特异性诱导 CD4+（EM）细胞增殖，表明它们可能具有补充 IL-7 免疫疗法的独特潜力。
